Arthritogenic Alphavirus Vaccines: Serogrouping Versus Cross-Protection in Mouse Models.

Wilson Nguyen,David Warrilow,Helen M Faddy,Thuy T Le,Eri Nakayama,Richard J N Allcock,Paul M Howley,Viviana P Lutzky,Liang Liu,Bing Tang,Natalie A Prow,John D Hayball,Daniel J Rawle,Roy A Hall,Kexin Yan,Andreas Suhrbier,Jody Hobson‐Peters ,Paul R Young ,Günter Härtel ,Thomas J Cooper ,Nidia M M Oliveira

doi:10.3390/vaccines8020209

Abstract

Chikungunya virus (CHIKV), Ross River virus (RRV), o’nyong nyong virus (ONNV), Mayaro virus (MAYV) and Getah virus (GETV) represent arthritogenic alphaviruses belonging to the Semliki Forest virus antigenic complex. Antibodies raised against one of these viruses can cross-react with other serogroup members, suggesting that, for instance, a CHIKV vaccine (deemed commercially viable) might provide cross-protection against antigenically related alphaviruses. Herein we use human alphavirus isolates (including a new human RRV isolate) and wild-type mice to explore whether infection with one virus leads to cross-protection against viremia after challenge with other members of the antigenic complex. Persistently infected Rag1-/- mice were also used to assess the cross-protective capacity of convalescent CHIKV serum. We also assessed the ability of a recombinant poxvirus-based CHIKV vaccine and a commercially available formalin-fixed, whole-virus GETV vaccine to induce cross-protective responses. Although cross-protection and/or cross-reactivity were clearly evident, they were not universal and were often suboptimal. Even for the more closely related viruses (e.g., CHIKV and ONNV, or RRV and GETV), vaccine-mediated neutralization and/or protection against the intended homologous target was significantly more effective than cross-neutralization and/or cross-protection against the heterologous virus. Effective vaccine-mediated cross-protection would thus likely require a higher dose and/or more vaccinations, which is likely to be unattractive to regulators and vaccine manufacturers.

Highlights

IntroductionThe arthritogenic alphaviruses that cause disease in humans include chikungunya virus (CHIKV), the Australian Ross River virus (RRV), the African o’nyong nyong virus (ONNV) and the South
The arthritogenic alphaviruses that cause disease in humans include chikungunya virus (CHIKV), the Australian Ross River virus (RRV), the African o’nyong nyong virus (ONNV) and the SouthAmerican Mayaro virus (MAYV) [1,2,3,4]
Using a newly identified human isolate of RRV from a transfusion case, RRVTT [53] characterized and human isolates of Chikungunya virus (CHIKV), ONNV and MAYV, we investigate the ability of infection with one alphavirus to mediate cross-protection against viremia in adult wild-type mice after subsequent infection with a heterologous alphavirus

Summary

Introduction

The arthritogenic alphaviruses that cause disease in humans include chikungunya virus (CHIKV), the Australian Ross River virus (RRV), the African o’nyong nyong virus (ONNV) and the South. American Mayaro virus (MAYV) [1,2,3,4]. Symptomatic infection with these viruses results in a series of rheumatic manifestations that usually include acute fever, rash and myalgia and an acute, and often chronic, polyarthritis/polyarthralgia [4]. RRV causes a mean of ≈4600 cases per annum (2000–2015) in Australia where it is a notifiable disease [7], with a large outbreak (estimated at >60,000 cases) occurring in The Pacific Islands in 1979/80 [3,8]. Recent outbreaks in the Shoalwater Bay Training Area in Australia (a major site of international military exercises) [9]

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